1. Field of Invention
This invention relates to photodynamic compounds useful as therapeutic agents and as in vivo diagnostic agents. In particular, the invention provides tunable metal-based thiophene photodynamic compounds that can be activated to cleave DNA upon irradiation with visible light by either a Type 1 or Type 2 photoprocess.
2. Description of Related Art
Photodynamic therapy (PDT) is currently an active area of research for the treatment of diseases associated with hyperproliferating cells such as cancer and non-malignant lesions. PDT has also found use in other contexts, including but not limited to the treatment of acne, psoriasis, proliferative non-malignant conditions, ulcers and wounds. The development of new photodynamic compounds (PDCs) (or photosensitizers (PSs)) for photodynamic therapy (PDT) has been increasingly focused on metallosupramolecular complexes derived from metals such as ruthenium and rhodium. The ongoing investigation of new PSs for PDT stems from the limitations associated with traditional organic-based porphyrins such as PHOTOFRIN, which must be activated with relatively short wavelengths of light and do not function in hypoxic environments. Significant advances have been made toward overcoming these limitations with the introduction of mixed-metal complexes that possess low-lying 3MMCT (metal-to-metal charge transfer) excited states. To date, however, there has been limited reporting of photodynamic compounds, particularly those with a mononuclear or dinuclear design, that are capable of providing photodynamic therapy for the treatment of diseases associated with hyperproliferating cells such as cancer and non-malignant lesions, and/or capable of treating other conditions including but not limited to infectious diseases and pathogen infections.
There is a long felt need for new photodynamic compounds (PDCs) that are useful as photosensitizers for PDT that are both disease-modifying and effective in treating patients with diseases caused by hyperproliferating cells, for example, cancer. There is also a long felt need for new PDCs that are useful as in vivo diagnostic agents. Moreover, it is desired to provide novel PDCs having: (1) increased photostability, (2) increased absorption at activation wavelength, (3) red-light, and preferably NIR, absorption, (4) maximal activity regardless of oxygen levels (possibly utilizing a mechanism for switching between type 1 and type 2 photosensitization), and (5) intracellular nuclear DNA targeting.
The present invention addresses the need to develop novel PDCs that are useful as photosensitizers for PDT that are both disease-modifying and effective in treating one or more of the conditions discussed above, such as treating patients with diseases caused by hyperproliferating cells, for example, cancer. The present invention also addresses the long felt need for new PDCs that are useful as in vivo diagnostic agents.
All references cited herein are incorporated herein by reference in their entireties.